Inflammation in Ischemic Stroke: Mechanisms, Consequences and Possible Drug Targets

Abstract

Ischemic stroke is caused when blood flow to the brain is hampered, leading to instant deficiency of nutrients and oxygen required for normal brain functioning. Reperfusion can alleviate damage from stroke if performed immediately after the onset of ischemia however the efficacy of reperfusion is tempered by secondary injury mechanisms. This multifarious sequence of events leads to the commencement of deleterious cycles of inflammation, oxidant stress and apoptosis that finally culminate in delayed death of neuronal cells even when the brain is effectively reperfused. Wealth of data from clinical as well as experimental studies points to a prominent role of inflammation in secondary injury. In this review we will discuss, in detail, the cellular and molecular mediators of inflammation and their possible therapeutic targets in both experimental and clinical forms of stroke.

Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin

“…A recent study by Choquet et al identified common genetic variations in inflammatory and immune response pathways in patients with fCCM that correlated with hemorrhage, lesion size and lesion number, strongly suggesting that genetic variation in the inflammatory response can influence disease severity and variability (Choquet et al, 2014b). Indeed, the connection between inflammation and hemorrhage is well established in multiple cerebrovascular disorders, including cerebral ischemia (Ahmad et al, 2014), congenital and trauma-induced aneurysm (Kataoka, 2015), cerebral arteriovenous malformation (AVM) (Mouchtouris et al, 2015), and cerebral amyloid angiopathy (Castro Caldas et al, 2015). Anti-inflammatory treatment of these conditions reduces bleed rate and severity.…”

Life and death in the trash heap: The ubiquitin proteasome pathway and UCHL1 in brain aging, neurodegenerative disease and cerebral Ischemia

“…Cerebral ischemia may impair UPP function via several mechanisms (Ahmad et al, 2014). Cerebral ischemia results in production of reactive oxygen species (ROS) generated via induction of free radical generating enzymes and mitochondrial dysfunction (Chen et al, 2011a; Ruszkiewicz and Albrecht, 2015).…”

“…Cerebral ischemia generates the formation of a number of reactive lipids, including carbonyl-containing species such as CyPgs (Ahmad et al, 2014; Figueiredo-Pereira et al, 2014). CyPgs can covalently modify the cysteine amino acid at 152 (C152) of UCHL1, reducing its activity and unfolding the enzyme resulting in protein aggregation (Kondo et al, 2002; Liu et al, 2015b).…”

Computer modeling of ischemic stroke

“…Immediately after the stroke, it is useful to reduce inflammation. At later times, inflammation is important for brain remodeling and restoration (Barone and Feuerstein, 1999; Ahmad et al, 2014). …”